Study of AMG 160 in Subjects With Non-Small Cell Lung Cancer

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects With Non-Small Cell Lung Cancer

This study aims to evaluate the safety and tolerability of AMG 160 and to evaluate the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D).

Study Overview

• Status: Terminated
• Conditions: NSCLC; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: AMG 160

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris OBrien Lifehouse
• Austria
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg
  • Wien, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Histologically or cytologically confirmed stage 4 or recurrent non-squamous NSCLC (Part 1); histologically or cytologically. confirmed stage 4 or recurrent NSCLC (Part 2 only, squamous cell histology/cytology allowed in Part 2).
• Without a driver mutation: disease progression following at least one line of prior chemotherapy and at least 1 prior anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapy.
• With a driver mutation must experience disease progression on at least 1 targeted therapeutic agent to be eligible.
• Detectable prostate-specific membrane antigen (PSMA) expression by PSMA positron emission tomography (PET)/computed tomography (CT) imaging.
• Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2.

Exclusion Criteria:

• Radiographic evidence of intratumor cavitation, major blood vessel invasion or encasement by cancer.
• Untreated or symptomatic brain metastases and leptomeningeal disease.
• History of hemoptysis within 3 months prior to first dose.
• History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease).
• Myocardial infarction, unstable angina, cardiac arrhythmias requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months prior to start of dosing.
• Vasculitis or grade 3/4 gastrointestinal bleeding within 3 months prior to first dose; vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months of first dose.
• Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to start of dosing.
• Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with treatment.
• Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).
• Chronic systemic corticosteroid therapy or any other immunosuppressive therapies unless stopped 7 days prior to first dose.
• Any biological therapy or immunotherapy within 3 weeks of start of first dose.
• Major surgery within 4 weeks of first dose.
• Infection requiring IV antimicrobials for management within 7 days of dosing.
• Known human immunodeficiency virus (HIV) infection, hepatitis C infection.
• Active autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Exploration; The dose exploration part of the study will estimate the MTD and/or the RP2D.	Drug: AMG 160; AMG 160 administered as an intravenous (IV) infusion
Experimental: Part 2: Dose Expansion - Cohort 1 Non-squamous NSCLC; Participants with non-squamous non-small cell lung cancer (NSCLC) will be administered the RP2D identified from the dose exploration part of the study.	Drug: AMG 160; AMG 160 administered as an intravenous (IV) infusion
Experimental: Part 2: Dose Expansion - Cohort 2 Squamous NSCLC; Participants with squamous NSCLC will be administered the RP2D identified from the dose exploration part of the study.	Drug: AMG 160; AMG 160 administered as an intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience One or More Dose-limiting Toxicities (DLT)	DLT were defined as any adverse event (AE) with an onset within first 28 days following first dose of AMG 160 meeting pre-specified criteria unless clearly attributable to causes other than AMG 160 treatment.	Day 1 to Day 28
Number of Participants Who Experience One or More Treatment-emergent AE (TEAE)	An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE is any AE that occurred on or after first dose of study treatment up to 30 days after the last dose or End of Study date or start of new anti-cancer therapy, whichever is earlier. A treatment-related TEAE is any TEAE that, per investigator review, has a reasonable possibility of being caused by the study treatment. Any abnormal vital signs measurement or clinical laboratory test result, including those that worsened from Baseline, that were considered clinically significant in the medical and scientific judgement of the investigator were reported as an AE.	Median (min, max) time from first dose to 30 days after the last dose, end of study or start of new anti-cancer therapy; whichever is earlier, was 66 (52, 100) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	ORR per modified RECIST v1.1 was defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment.; CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm.; PR: Decrease of 30% or greater in tumor burden compared with baseline. CR/PR must have been confirmed at least 4 weeks later. Exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Overall Survival (OS)	Overall survival (OS) was defined as the time from the date of study Day 1 until death due to any cause. OS time (months) = (date of death - study Day 1 + 1) x 12/365.25. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and percentiles were using Greenwood's formula to estimate the standard error of the landmark estimates using the method by Kalbfleisch and Prentice (1980).	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Radiographic Progression Free Survival (PFS) Per Modified RECIST v1.1	Radiographic PFS per modified RECIST v1.1 was defined as the interval from study Day 1 to the earlier of a radiographic progressive disease (PD) or death from any cause, based on investigator assessment; otherwise, radiographic PFS was censored at the last evaluable tumor assessment date. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Clinical PFS Per Modified RECIST v1.1	Clinical PFS per modified RECIST v1.1 was defined as the interval from study Day 1 to the earlier of a clinical PD or death from any cause, based on investigator assessment; otherwise, clinical PFS was censored at the last evaluable tumor assessment date. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Time to Response Per Modified RECIST v1.1	Time to response per modified RECIST v1.1 was defined as the interval from study Day 1 to the either CR or PR based on investigator assessment.; CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm.; PR: Decrease of 30% or greater in tumor burden compared with baseline. CR/PR must have been confirmed at least 4 weeks later.	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Time to Progression Per Modified RECIST v1.1	Time to progression per modified RECIST v1.1 was defined as the interval from study Day 1 to PD, based on investigator assessment. Time to progression was censored at the last evaluable post-baseline tumor assessment prior to subsequent anti-cancer therapy; otherwise at study Day 1. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Time to Clinical Progression	Time to clinical progression was defined as the interval from study Day 1 to PD. Time to clinical progression was censored at the last evaluable post-baseline tumor assessment prior to subsequent anti-cancer therapy; otherwise at study Day 1. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Duration of Response (DOR) Per Modified RECIST v1.1	DOR was defined as the time from the date of an initial objective response per modified RECIST v1.1 to the earlier of soft-tissue progression or death based on investigator assessment.; CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm.; PR: Decrease of 30% or greater in tumor burden compared with baseline. CR/PR must have been confirmed at least 4 weeks later. Participants who had not ended their response at the time of analysis had DOR censored at their last evaluable tumor assessment by CT/MRI scan.	Median (min, max) time from first dose to end of study was 100 (94, 122) days
Time to Subsequent Therapy	Time to subsequent therapy was defined as the time from study Day 1 to the time a participant started/received the subsequent cancer therapy/subsequent therapy; otherwise time to subsequent therapy was censored at the last known date of any of the study assessment prior to initiating the subsequent cancer therapy/subsequent therapy. Subsequent therapy was defined any anti-cancer therapies intended to treat NSCLC, or any other anti-cancer therapies started after ending study treatment and prior to End of Study. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).	Median (min, max) time from first dose to end of study was 100 (94, 122) days

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Actual): December 8, 2021
• Study Completion (Actual): January 26, 2022

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Phase 1b; AMG 160
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 20180273

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No